tbuckley/cabot-search huggingface dataset:
Neoadjuvant pegylated liposomal doxorubicin (PLD) plus cyclophosphamide followed by nab-paclitaxel (Nab-P) as primary chemotherapy continuously combined with dual HER2 blockage for HER2-positive breast cancer: A single-arm phase 2 trial (Brecan Trial).
Authors: Jixin Yang, Yuqing Yang, Xinxin Wen, Jiang Wu, Jing Yu, Lei Wang, Meiling Huang, Wenyu Hu, Wen Ma, Nanlin Li
Journal: Journal of Clinical Oncology (2022)

e12622 Background: Despite that AC-THP regimen is one of the commonly used regimens for neoadjuvant treatment of HER2-positive breast cancer, previous studies showed that pCR rate rarely exceeds 70%. We hypothesized that prolonged dual anti-HER2 therapy can increase pCR rate in neoadjuvant therapy. In this study, we designed a single-arm trial of ACHP-THP regimen (continuous dual anti-HER2 therapy of trastuzumab and pertuzumab) in neoadjuvant therapy of HER2 positive breast cancer. To minimize adverse cardiovascular events, we used pegylated liposomal doxorubicin (PLD) and Nab-Paclitaxel (Nab-P) instead of doxorubicin and paclitaxel. We aimed to examine whether continuous dual anti-HER2 therapy can boost pCR rate in the neoadjuvant therapy. The cardiotoxicity was closely monitored when the anti-HER2 therapy was combined with PLD and Nab-P respectively. Methods: Upon approval by the Medical Ethics Committee of Xijing Hospital, patients with HER2-positive breast cancer (cT2-3/N0-1/M0) receiving neoadjuvant therapy, were enrolled. The patients were treated with PldCHP (pegylated liposomal doxorubicin 35mg/m 2 , cyclophosphamide 600mg/m 2 , trastuzumab 8 mg/kg loading, then 6 mg/kg, pertuzumab 840 mg loading, then 420 mg, iv, q3w) for 4 cycles followed by Nab-PHP (Nab-Paclitaxel 260mg/m 2 , trastuzumab 6 mg/kg, pertuzumab 420 mg, iv, q3w) for 4 cycles, with strict monitoring of cardiotoxicity. The primary endpoint was pCR rate, and secondary endpoint was cardiotoxicity during neoadjuvant therapy. Results: From January 2020 to October 2021, a total of 96 patients were recruited. Among the 96 patients with a median age of 49 (21-71), 58 patients were HR positive and 42 patients had positive lymph node status. Overall, the pCR rate was 80.2% (77/96). The ER-positive tumor achieved a higher pCR rate than ER-negative tumor (82.8% vs 76.3%, p=0.439), but the difference was statistically insignificant. Multivariate regression analysis showed that for participants older than 30, HER2 3+ (IHC) showed a statistically significant positive influence on pCR rate. The common adverse reactions of grade ≥3 were neutropenia (30.2%), asthenia (8.3%), and peripheral sensory neuropathy (7.3%). Left ventricular insufficiency was detected in 4 patients, and no cardiotoxic events higher than grade 2 occurred during the neoadjuvant therapy. There was no treatment-related death. Conclusions: The PldCHP---Nab-PHP regimen is a feasible and effective neoadjuvant therapy for early stage HER2-positive breast cancer, showing high pCR rate and acceptable cardiotoxicity. These results support a further random controlled trial testing for continuous dual anti-HER2 therapy combined with PLD in neoadjuvant or adjuvant therapy of HER2 positive breast cancer.
Epigenetic age acceleration in U.S. testicular cancer survivors (TCS).
Authors: Yinan Zheng, Jun Wang, Paul C. Dinh, Katherine L. Nathanson, Benita Weathers, Linda A. Jacobs, David J. Vaughn, Lifang Hou, Lois B. Travis
Journal: Journal of Clinical Oncology (2022)

5033 Background: Given the young age at diagnosis and effective therapies (cisplatin-based chemotherapy and/or surgical approaches), most TCS gain many decades of life. Attention has been drawn to the potential downsides of these treatment successes, including the accelerated development of age-related diseases. Previous studies have suggested that cytotoxic treatment and carcinogenesis are associated with epigenetic changes, leading to premature biological aging processes. Methods: We recruited 24 TCS managed with surgical approaches alone and 24 cisplatin-treated TCS (all also treated with surgical removal of the cancerous testis) and who had histologic/serological germ cell tumor diagnosis before 55 years, and were disease-free at routine follow up. We also included 310 cancer-free race- and age-matched (+/- 5 years) males from a normative cohort, i.e., the Coronary Artery Risk Development in Young Adults (CARDIA) Study. We undertook genome-wide interrogation of blood DNA methylation (DNAm) using the Illumina Infinium Methylation EPIC BeadChip (EPIC array). We quantified aging using DNAm GrimAge, a validated, composite biomarker consisting of DNAm surrogate biomarkers of seven plasma proteins associated with various age-related conditions plus a DNAm surrogate of smoking pack-years. The comparison analysis was adjusted for age, race, smoking status, blood cell type proportions estimated using DNA methylation batch effect, and other laboratory-related technical factors. Results: The median chronological age of TCS was 28 years (range 19-64) with 25% smokers. Compared to their chronological age, TCS managed with surgical approaches alone had a mean GrimAge of 39.4 years (i.e., 9.2 years older, paired t-test P = 0.001), and cisplatin-treated TCS had a mean GrimAge of 45.2 years (i.e., 14.9 years older, paired t-test P &lt; 0.001). Compared to the matched CARDIA controls, TCS managed with surgical approaches alone were on average 3.0 years epigenetically older (P = 0.093), and cisplatin-treated TCS were on average 11.2 years epigenetically older (P &lt; 0.001), suggesting an increasing trend with treatment burden (P-trend &lt; 0.001). Conclusions: Our data showed a faster epigenetic aging process in TCS. Consistent with previous studies, our data is in line with the hypothesis that TC cytotoxic treatment may induce premature aging. Although TCS managed with surgical approaches alone had no exposure to cytotoxic drugs, their epigenetic age may also be accelerated due to TC development and/or risk factors that contributed to it as well as post-therapy factors.
Prognostic impact of perioperative circulating levels of Insulin-like growth factor-I (IGF-I) and its binding proteins, IGFBP-2 and IGFBP-3, on disease outcomes after radical cystectomy
Authors: R. Sari Motlagh, V. Schuettfort, K. Mori, S. Katayama, P. Rajwa, A. Aydh, N. Grossmann, E. Laukhtina, B. Pradere, H. Mostafai, F. Quhal, M. Abufaraj, R. Lee, P. Karakiewicz, Y. Lotan, E. Comprate, M. Moschini, P. Gontero, S. Shariat
Journal: European Urology (2022)
Phase II study SECOMBIT (sequential combo immuno and target therapy study): A subgroup analysis with a longer follow-up.
Authors: Paolo Antonio Ascierto, Mario Mandalà, Pier Francesco Ferrucci, Massimo Guidoboni, Piotr Rutkowski, Virginia Ferraresi, Ana Maria Arance, Michele Guida, Evaristo Maiello, Helen Gogas, Erika Richtig, Maria Teresa Fierro, Celeste Lebbe, Hildur Helgadottir, Ignacio Melero Bermejo, Giuseppe Palmieri, Diana Giannarelli, Antonio Maria Grimaldi, Reinhard Dummer, Vanna Chiarion-Sileni
Journal: Journal of Clinical Oncology (2022)

9535 Background: To investigate the best sequential strategy, we started the SECOMBIT study, a randomized three parallel arms phase 2 study (NCT02631447). We used the combination of encorafenib/binimetinib (E+B) as targeted therapy (T-T) and the combination of ipilimumab/nivolumab (I+N) as immunotherapy (I-O). We explored the two different sequences and the “sandwich” strategy with a short course of target therapy, switched by combo immunotherapy at the best response, and not at progression of disease. In our previous report we have observed a trend in favor of the arms where I-O was given as first, confirmed by the first report of the DreamSeq study, a phase III study which compared the two different sequences with T-T and I-O. Here we updated the study data with a subgroup analysis. Methods: From Nov 2016 to May 2019, 37 centers in 9 countries enrolled 251 patients with untreated, metastatic BRAFV600 melanoma. Patients were randomized to Arm A [E+B until PD, followed by I+N], or Arm B (I+N until PD, followed by E+B) or Arm C (E+B for 8 weeks, followed by I+N until PD, followed by E+B). The overall survival (OS) is the primary endpoint of the study. Secondary endpoints included total progression-free survival (tPFS), 2- and 3-years survival rate, best overall response rate, duration of response, biomarkers evaluation. Results: The study primary endpoint was met in each arm with at least 30 patients alive at 24 months. The median follow-up estimated with the reverse Kaplan-Meier method was 37.1 months (IQR: 32.8-46.4). The OS at 2 and 3 years was calculated in the three arms for all patients, and in the subgroups normal or elevate LDH level and &lt; 3 or ≥ 3 metastatic sites. OS and tPFS rates at 2 and 3 years are shown in the table. Conclusions: With a 37.1 months median follow-up, 2 and 3-years OS as well as tPFS rates are higher in Arm B and C. In line with recent findings, the SECOMBIT results confirm a better trend in favor of Arm B and C treatment sequence. The analysis of the secondary endpoints is ongoing. Clinical trial information: NCT02631447. [Table: see text]
Medications mostly associated with haematuria: Assessment of the EudraVigilance (EV) and Food and Drug Administration (FDA) Pharmacovigilance databases entries
Authors: L.M. Rovesti, A. Nacchia, F. Di Giacomo, G. Disabato, C. Gravina, G. Gallo, J. Stira, B. Turchi, A. Guercio, R. Lombardo, A. Cicione, O.A. Voglino, V. Baldassarri, G. Guarnotta, E. Mancini, A. Franco, S. D'Annunzio, A. Tubaro, C. De Nunzio
Journal: European Urology (2022)
The adding value of COntrolling NUTritional status (CONUT) score to pre-operative counselling on significant early loss of renal function after radical nephrectomy for cancer
Authors: L. Ongaro, M. Boltri, F. Claps, F. Vianello, O. Lenardon, F. Visalli, L. Buttazzi, D. Maruzzi, F. Migliozzi, N. Pavan, G. Liguori, C. Trombetta
Journal: European Urology (2022)
EPID-04. PREDCAP, the French registry of predisposition to pediatric cancers
Authors: Lea Guerrini-Rousseau, Pauline Hoarau, Gaelle Bougeard, Lisa Golmard, Chrystelle Colas, Marion Gauthier-Villars, Claude Houdayer, Thierry Frebourg, Franck Bourdeaut, Laurence Brugieres
Journal: Neuro-Oncology (2022)

Abstract A pathogenic or likely pathogenic variant (PV) in a major cancer predisposition gene is identified in almost 10% of children or young adults who developed a cancer, regardless of their family history. This incidence may increase by the development of wide tumor sequencing programs leading to identify germline PVs in cancer patients and new cancer predisposition syndromes (CPS) associated with childhood cancers. Due to the rarity of each CPS, we still lack information about phenotype associated with most CPS especially cancer risks according to age as well as tumor characteristics and response to treatment. Within the French genetic multidisciplinary network involving pediatric oncologists, oncogeneticists and researchers, we have created a clinico-molecular registry for pediatric-CPS according to data protection regulation. The PREDCAP database collects clinical, genetic and molecular data from patients who developed pediatric tumors associated with a CPS, both retrospectively and prospectively. It includes a mandatory set of data on clinical phenotype, tumor characteristics (including treatment and outcome), family data and results of genetic analyses, with annual data updates. Interoperability with existing databases is planned, allowing for pooling of data collection and management. Aims of PREDCAP registry are to obtain reliable clinical and molecular data on pediatric CPS with a simplified and effective access. By collecting all available data on a large number of patients thanks to international collaborations, we hope to improve the knowledge on rare CPS, in particular, to better define the tumor spectrum and the penetrance of PVs, to analyze the specificity of tumors associated with these germline PVs. With this tool, we wish to facilitate future projects using structured and centralized data, associated with a virtual bank of available tumor and constitutional DNA, to evaluate and improve the relevance of management recommendations established for each syndrome.
Cost effectiveness of reduced intensity conditioning and transplantation of unrelated umbilical cord blood versus HLA haploidentical related bone marrow for adults with hematologic malignancies.
Authors: Lotte Maria Gertruda Steuten, Aasthaa Bansal, Li Li, Claudio G Brunstein, Paul V. O'Donnell, Mary Eapen, Lindsey R. Sangaralingham, Viengneesee Thao, Joshua A. Roth, Winona E Wright, Scott David Ramsey
Journal: Journal of Clinical Oncology (2022)

6591 Background: BMT CTN 1101 was a Phase III randomized controlled trial evaluating the comparative effectiveness of unrelated umbilical cord blood (UCB) versus HLA-haploidentical related donor bone marrow (haplo-BM) cell sources for hematopoietic cell transplantation (HCT) in patients with high-risk hematologic malignancies (leukemias, lymphomas). We report results of an economic evaluation conducted as part of the clinical trial. Methods: 368 patients (90% of planned accrual) enrolled from 33 centers in the U.S. were randomly assigned to unrelated UCB (n=186) or haplo-BM (n=182) transplant. Healthcare utilization and costs were estimated using propensity-score matched cohorts of BMT patients in the OptumLabs Data Warehouse for trial participants &lt;65 years, and Medicare claims for trial participants ≥65 years. Cost-effectiveness was calculated from payer perspectives (commercial, Medicare) over a 20-year time horizon from time of transplant. Weibull models (best fit based on AIC/BIC) were used to extrapolate survival from 5-year trial follow-up data. Trial participant surveys (EQ-5D) were used to derive health state utilities for estimating Quality-Adjusted Life Years (QALYs). One-way and probabilistic sensitivity analyses were conducted to assess uncertainty in results. Outcomes were discounted at 3% annually. Results: At 5-year follow-up, overall survival was 42% for haplo-BM versus 36% for UCB (P=.06). Over a 20-year time horizon, haplo-BM is expected to be more effective and more costly for &lt;65 year-olds and in ≥65 year-olds it is expected to be more effective and less costly. In one-way uncertainty analyses, for persons &lt;65, the cost/QALY result was most sensitive to life years and health state utilities. For persons ≥65, life years were more influential than costs and health state utilities. Using probabilistic sensitivity analysis, for persons &lt;65 there was a 43% chance that haplo-BM was cost-effective using a willingness to pay threshold of $150k/QALY and 52% at a $200K/QALY threshold. Conclusions: Results from a large national clinical trial indicate that compared to UCB, haplo-BM was moderately cost-effective for patients aged &lt;65 years, and less costly and more effective for persons ≥65 years. Haplo-BM is a fair value choice for commercially insured patients with high-risk leukemia and lymphoma who require HCT. For Medicare enrollees, haplo-BM is a preferred choice when considering costs and outcomes. [Table: see text]
DIPG-63. Therapies for diffuse gliomas in pediatric patients: a systematic review and meta-analysis
Authors: Awais Paracha, Mohamed S Abdelbaki, Pournima Navalkele
Journal: Neuro-Oncology (2022)

Abstract Diffuse gliomas are one of the most challenging pediatric brain tumors of the current era. The new WHO classification has brought in a paradigm shift in the diagnosis and management of diffuse gliomas. Although these tumors are not surgically resectable, an integrated molecular analysis could make them more amenable to targeted agents. We conducted a thorough systematic review and meta-analysis of therapies for diffuse gliomas in pediatric patients. Methods: Using PRISMA guidelines, PubMed, (Medline), Cochrane, and Google Scholar database searches are being conducted using search terms “diffuse midline glioma”, “diffuse midline astrocytoma” and “diffuse glioma management”. PubMed search filters used to find relevant articles were “human” species, “English” language, and “age birth to 18 years”. Results: Interim analysis using the PubMed database has revealed 387 articles of which 32 articles describe details of therapies used in pediatric patients. We found 8 case reports, 17 case series, and 7 clinical trials elucidating therapies for diffuse gliomas. Comprehensive analysis of modalities of therapies including neurosurgery, chemotherapy, and radiation therapy, along with survival analysis for these patients stratified by H3.3K27M mutant status is ongoing.
Coupling gamified continuing education with confidence-based assessment to address knowledge gaps and assess attitudes towards liquid biopsy for cancer screening among primary care providers.
Authors: Jillian L Scavone, Katie Robinson, Emily Scully, Simon Cooper, Robert A. Esgro, Eric A. Klein
Journal: Journal of Clinical Oncology (2022)

11012 Background: Blood-based liquid biopsy assays offer a simplified approach to detect cancer early, guide clinical decision making, and predict treatment success. Given their novelty, primary care providers need education to improve knowledge and confidence regarding their use. The use of gamification in continuing medical education (CME) has been shown to increase engagement and knowledge transfer, and confidence-based learning can improve the educational experience by identified areas in which learners lack comfort. Methods: We provided a gamified CME activity based on the principles of confidence-based learning designed to educate primary care providers (PCPs) on the latest advances regarding the use of liquid biopsy for cancer screening. The game coupled knowledge questions with self-assessment of confidence to gage awareness of these topics. Pre- and post-test was used to quantify the impact of the education. The CE activity was available for credit from March 31, 2021 to March 31, 2022. Results: As of January 2022, 389 PCPs have participated. Overall, participants scored an average 76% on gaming questions related to the rationale behind the use of cell free DNA (cfDNA) for cancer screening and the benefits of liquid biopsy over tissue biopsy, demonstrating relatively high baseline knowledge on these topics. Self-reported confidence among those who answered correctly, however, was only 3.4 out of 5.0, suggesting a lack of comfort with the concepts despite answering correctly. On topics related to specific studies that demonstrated the clinical utility of liquid biopsy, participants scored only 59% and confidence scored averaged 3.17 out of 5.0, demonstrating a lack of knowledge and comfort on these topics. Across all topics, providers scored a 61% on a pre-test. Post-learning, providers scored 89%, highlighting the impact of the education on knowledge gaps. Moreover, while 52% of participants had never ordered a liquid biopsy for cancer screening prior to the education, 69% report being likely or extremely likely to do so because of the education provided. Conclusions: Integration of gamified and confidence-based learning into CE activities is an impactful way to identify and address knowledge gaps while also informing the need for future education. In this study, while self-report of confidence generally correlated with knowledge scores, confidence scores were only average even among those who answered correctly, demonstrating the need for skills-based learning that may improve comfort with liquid biopsy in the clinical setting.
A single center phase 2 study of anti-PD-1 antibody plus bevacizumab and FOLFIRI as second-line treatment for patients with MSI-H metastatic colorectal cancer.
Authors: Hongli Li, Tao Ning, Le Zhang, Shaohua Ge, Yuchong Yang, Ming Bai, Xia Wang, Zhi Ji, Rui Liu, Ting Deng, Yi Ba
Journal: Journal of Clinical Oncology (2022)

e15541 Background: The therapeutic efficacy of second-line chemotherapy for metastatic colorectal cancer (mCRC) is low. Immunotherapy is suitable for MSI-H mCRC, but the efficacy of single-drug immunotherapy is still unsatisfactory. We investigated to combine immunotherapy with bevacizumab and FOLFIRI as second-line treatment for these patients. Methods: This single center exploratory phase 2 study enrolled adults patient with histologically confirmed metastatic colorecal adenocarcinoma, who were failure of oxaliplatin-based chemotherapy as first-line therapy. Patients receive FOLFIRI (iritecan 180mg/m 2 , leucovorin 400mg/m 2 , fluorouracil 400mg/m 2 bolus, fluorouracil 2400mg/m 2 46-48 hours), anti-PD-1 antibody (Nivolumab 240mg, or Pembromab 200mg, or Terriprizumab 240mg), and bevacizumab (5mg/kg). Maintenance therapy was allowed using PD-1, bevacizumab and/or fluorouracil. An-PD-1 antibody is given for up to 24 months. Results: Between November 29,2018 and January 15, 2021, a tolal of 8 patients were enrolled in our study. There were 3 femles and 5 males, and the median age was 39.5 years old. Among 8 patients who were evaluated, complete resonse (CR) was obtained in 3 cases, partial response (PR) was observed in 3 cases, and stable disease (SD) in 2 cases. Objective response rate was 75%, and disease control rate was 100%. The median PFS and the median overal survival have not yet been reached. The most common adverse events (AE) were alopecia (87.5%), nausea (75%), vomit (50%), hypothyroidism (50%), leukopenia (37.5%), hypertension (25%) and proteinuria (25%). Most of the AEs were grade 1 or 2, and the most common grade 3 or 4 treatment-related AE was hypertension (25%). Conclusions: Anti-PD-1 antibody plus bevacizumab and FOLFIRI demonstrated promising activity as second-line treatment for patients with MSI-H metastatic colorectal cancer. Clinical trial information: NCT05035381.